RESEARCH ARTICLE


Suppression of PAMPs, Pathogen-Associated Microbial Patterns, Induced Cytokine Synthesis of PBMC, Human Blood Mononuclear Cells, by Immunoglobulin Preparation



Ayumi Yamamoto1, Noriko N. Miura1, Toshiaki Oharaseki2, Kei Takahashi2, Shiro Naoe2, Kazuo Suzuki3, Naohito Ohno*, 1
1 Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
2 Department of Pathology, Toho University Ohashi Medhcal Center, 2-17-6 Ohashi, Meguro, Tokyo 153-8515, Japan
3 Inflammation Program, Department of Immunology, Chiba University Graduate School of Medicine, 1-8-1 Ihana, Chuo-ku, Chiba, Chiba 260-8670, Japan

Article Information


Identifiers and Pagination:

Year: 2012
Volume: 5
First Page: 53
Last Page: 61
Publisher Id: TOALLJ-5-53
DOI: 10.2174/1874838401205010053

Article History:

Received Date: 20/6/2012
Revision Received Date: 15/7/2012
Acceptance Date: 17/7/2012
Electronic publication date: 24/8/2012
Collection year: 2012

© 2012 Yamamoto et al;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192- 0392, Japan; Tel./Fax: +81-42-676-5561; E-mail: ohnonao@toyaku.ac.jp


Abstract

The applications of immunoglobulin preparation for intravenous injection (IVIg) for various intractable diseases are increasing. The two major clinical indications for IVIg are the replacement therapy and the anti-inflammation therapy for a variety of acute and chronic autoimmune diseases. One of the proposed mechanisms of IVIg activity is the modulation of cytokine expression and function; therefore, we analyzed the effect of IVIg on pathogen-associated molecular pattern (PAMP)-induced cytokine production by peripheral blood mononuclear cells (PBMCs). The production of tumor necrosis factor-α (TNF-α) as a result of stimulation with lipopolysaccharide (LPS), polyinosinic-polycytidylic acid sodium salt (Poly I:C), or Pam3CysSerLys4 (Pam3) was significantly inhibited by sulfonated-IVIg (S-IVIg), or by F(ab')2. Assessed by one-color microarray analysis, the expressions of 229 genes were inhibited to 1/200 or less by F(ab')2. On the other hand, the expressions of 159 genes were increased by more than 100-fold by F(ab')2. According to these results, it was suggested that IVIg inhibits inflammatory PAMPs-induced cytokine production by PBMCs, due to the modulation of varieties of gene expression.

Keywords: anti-inflammatory effect, intravenous immunoglobulin (IVIg) therapy, microarray analysis, pathogen-associated microbial patterns (PAMPs), peripheral blood mononuclear cell (PBMC).